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Conjunctival lymphangiomas are rare hamartomas of lymphatic origin that are usually located in the bulbar conjunctiva. They commonly present either as focal or diffuse bulbar chemosis or as dilatation of lymphatic vessels that resembles an isolated cyst or a group of cysts. There can be bleeding inside the lymphangioma resulting in "chocolate cysts".1 We report the unusual case of a conjunctival lymphangioma on a 36 year-old male that presented as a large horn-like protruding structure. The lesion was surgically removed with simple excision associated with cryotherapy to the lesion's borders, as malignancy could not be ruled out preoperatively. Histopathological examination revealed a lymphangioma composed of an ill-defined proliferation of dilated lymphatic channels in the lamina propria, underlying conjunctival epithelium with squamous metaplasia, acanthosis and hyperkeratosis. One year postoperatively, the patient remains asymptomatic and without recurrence of the lesion.
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Neoplasias da Túnica Conjuntiva , Linfangioma , Humanos , Masculino , Neoplasias da Túnica Conjuntiva/diagnóstico , Neoplasias da Túnica Conjuntiva/cirurgia , Neoplasias da Túnica Conjuntiva/patologia , Adulto , Linfangioma/diagnóstico , Linfangioma/cirurgia , Linfangioma/patologia , Túnica Conjuntiva/patologia , Túnica Conjuntiva/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Diagnóstico DiferencialRESUMO
This case report discusses the finding of early cataract after pars plana vitrectomy in a patient with a history of rhegmatogenous retinal detachment.
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Catarata , Vitrectomia , Humanos , Vitrectomia/efeitos adversos , Masculino , Feminino , Complicações Pós-Operatórias , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , IdosoRESUMO
Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide an unique tool to address these questions but studies are scarce. We report a differentiation system toward enterocytes and goblet cells, the two major colonic epithelial cell lineages, using colon organoids generated from healthy tissue of colorectal cancer patients. Culture of these organoids in medium lacking stemness agents resulted in a modest ultrastructural differentiation phenotype with low-level expression of enterocyte (KLF4, KRT20, CA1, FABP2) and goblet cell (TFF2, TFF3, AGR2) lineage markers. BMP pathway activation through depletion of Noggin and addition of BMP4 resulted in enterocyte-biased differentiation. Contrarily, blockade of the Notch pathway using the γ-secretase inhibitor dibenzazepine (DBZ) favored goblet cell differentiation. Combination treatment with BMP4 and DBZ caused a balanced strong induction of both lineages. In contrast, colon tumor organoids responded poorly to BMP4 showing only weak signals of cell differentiation, and were unresponsive to DBZ. We also investigated the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on differentiation. Calcitriol attenuated the effects of BMP4 and DBZ on colon normal organoids, with reduced expression of differentiation genes and phenotype. Consistently, in normal organoids, calcitriol inhibited early signaling by BMP4 as assessed by reduction of the level of phospho-SMAD1/5/8. Our results show that BMP and Notch signaling play key roles in human colon stem cell differentiation to the enterocytic and goblet cell lineages and that calcitriol modulates these processes favoring stemness features.
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Proteína Morfogenética Óssea 4 , Calcitriol , Proteínas de Transporte , Diferenciação Celular , Colo , Dibenzazepinas , Células Caliciformes , Fator 4 Semelhante a Kruppel , Organoides , Receptores Notch , Transdução de Sinais , Humanos , Organoides/efeitos dos fármacos , Organoides/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proteína Morfogenética Óssea 4/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/citologia , Colo/patologia , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Calcitriol/farmacologia , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/metabolismo , Dibenzazepinas/farmacologia , Linhagem da Célula/efeitos dos fármacos , Enterócitos/metabolismo , Enterócitos/efeitos dos fármacos , Enterócitos/citologia , Vitamina D/farmacologiaRESUMO
Candida albicans is a pathobiont in humans that forms part of the mycobiota in healthy individuals and can cause different pathologies upon alterations of the host defenses. The mammalian gut is clinically relevant as this niche is the most common pool for bloodstream-derived infections. The ability of C. albicans to switch from yeast to hypha has been related to the commensal-to-pathogen transition and is, therefore, considered relevant in virulence. Recently, filaments have been implicated in the humoral response in the gut. C. albicans exhibits other morphologies that play different roles in pathogenicity and commensalism. This review focuses on the role of these morphological transitions in C. albicans proliferation and its establishment as a commensal in the mammalian gut, paying special attention to the transcription factors involved in their regulation.
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Candida albicans , Fatores de Transcrição , Animais , Humanos , Fatores de Transcrição/genética , Simbiose , Virulência , Regulação Fúngica da Expressão Gênica , Proteínas Fúngicas/metabolismo , Mamíferos/metabolismoRESUMO
INTRODUCTION: Single-haptic iris-claw intraocular lens (IOL) dislocation is not an uncommon complication. A few different surgical techniques are available for its refixation but usually involve a more invasive approach. We aim to demonstrate an original and simple approach for refixation of single haptic retropupillary iris-claw IOL subluxations. METHODS: We present a case of an 80-year-old male with a single haptic retropupillary iris-claw IOL subluxation in a previously vitrectomized eye. We used a new surgical approach to refix this type of subluxation. RESULTS: This new technique uses only two 30-gauge needles (one of them connected to a viscosurgical device) to re-enclavate the subluxated haptic of the retropupillary iris-claw IOL. By minimising surgical manipulation, the patient's postoperative period was uneventful. CONCLUSIONS: We highlight a new, quick, safe, and unusual surgical approach to single-haptic retropupillary iris-claw IOL dislocation in vitrectomized eyes. Because of its characteristics, we named it the "fencing" IOL repositioning technique.
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Migração do Implante de Lente Intraocular , Iris , Lentes Intraoculares , Humanos , Masculino , Idoso de 80 Anos ou mais , Iris/cirurgia , Migração do Implante de Lente Intraocular/cirurgia , Acuidade Visual/fisiologia , Reoperação , Implante de Lente Intraocular/métodos , Vitrectomia/métodos , Desenho de PróteseRESUMO
Optic neuropathies, such as glaucoma, are some of the leading causes of irreversible blindness worldwide. There has been a lot of research for potential therapies that could attenuate and even reduce the impact of the pathological pathways that lead to the loss of retinal ganglion cells (RGCs). In recent years, vitamin B3 (nicotinamide) has gained some interest as a viable option for these neurodegenerative diseases due to its fundamental role in enhancing the mitochondria metabolism of the RGCs. This review focuses on elucidating the impact of vitamin B3 on retinal cells, especially when in a dysfunctional state like what happens in optic neuropathies, especially glaucoma. This review also summarizes the existing and future research on the clinical effects of vitamin B3 in these optic neuropathies, and determines appropriate recommendations regarding its dosing, efficacy, and eventual side effects.
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Glaucoma , Doenças do Nervo Óptico , Humanos , Doenças do Nervo Óptico/tratamento farmacológico , Doenças do Nervo Óptico/etiologia , Glaucoma/metabolismo , Células Ganglionares da Retina/metabolismo , Vitaminas , Suplementos NutricionaisRESUMO
BACKGROUND: Neurotropic capabilities of SARS-COVs allow viruses to reach the central nervous system by hematogenous neuronal dissemination. The human retina, as an extension of the Central Nervous System, may have some neurodegenerative and/or vascular modifications related to COVID-19. OBJECTIVES: To evaluate choroidal and inner neural layers in participants previously recovered from COVID-19 compared to the control group using optical coherence tomography. METHODS: With a cross-sectional approach, the sample (n = 96), constituted by patients who have recovered from COVID-19 (n = 56) and healthy participants control group (n = 40) were ophthalmologically characterized. The neurodegenerative and vascular histological assessment was performed using SD-OCT and the mean thickness was measured in Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Retinal nerve fiber layer, Ganglion cell layer and subfoveal choroidal thickness were obtained through semi-automatic measurement. RESULTS: A total of 40 controls (27 women [67.5%]) and 56 COVID-19 participants (34 women [60.8%]) were included in this first report. There were retinal thickness significant differences in nearly all inner ETDRS subfields: nasal 3 mm (p = .025), I3 (p = .049), and temporal 3 mm (p = .009). Also, a decrease in neural layers was found in the nasal 3 mm (p = .049) and temporal 3 mm (p = .029) during ganglion cell layer assessment. The peripapillary retinal nerve fiber layer thickness was thinner in the COVID-19 group in superior temporal (p = .019), nasal (p = .002), inferior temporal (p = .046) and global (p = .014). Concerning the subfoveal choroidal measurement, an increase was observed in the COVID-19 group (p = .002). CONCLUSION: Participants who had recovered from COVID-19 showed a non-glaucomatous neuropathy trend pattern. We found differences closer to the classic description of the "bow-tie" observed in other neurological as compressive neuropathies at the chiasma location. OCT assessment also showed an increase in choroidal thickness as a result of vascular changes.
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COVID-19 , Células Ganglionares da Retina , Humanos , Feminino , Células Ganglionares da Retina/patologia , COVID-19/patologia , Retina/patologia , Corioide/patologia , Tomografia de Coerência Óptica/métodosRESUMO
It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin-angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.
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Captopril , Hipertensão , Ratos , Animais , Ratos Endogâmicos SHR , Captopril/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Hipotálamo , Aminopeptidases , Lobo FrontalRESUMO
Introduction: Previously we have reported a r16S gene next generation sequencing study on the effect of high fat diets in the intestinal microbiota using a murine model. However, many important microbial traits occur at strain level and, in order to detect these population changes, culture-dependent approaches need to be applied. With this goal, we decided to study a very well-known commensal genus, Enterococcus, and therefore, intestinal enterococci methodically isolated during the above-mentioned experiment were analyzed. Materials and methods: A collection of 75 distinct enterococcal strains isolated from feces of mice fed a standard diet or high-fat diets enriched with butter, refined olive oil, or extra virgin olive oil and after 0, 6 or 12 weeks of diet, were genetically and phenotypically characterized in search of virulence factors, biogenic amine production and antibiotic resistance. All strains were tested for the susceptibility in vitro to two virgin olive oil polyphenols, oleuropein (the bitter principle of olives) and hydroxytyrosol (derived from oleuropein by enzymatic hydrolysis and responsible for the high stability of olive oil). Results: No drastic polyphenol effect was found except at high concentrations. However, when carrying out a comparative statistical study in the 75 strains of the collection according to the different diets, we have detected significant differences between the strains isolated from mice fed with a diet enriched with virgin olive oil and the rest of the diets. EVOO strains also presented less resistance to antibiotics and a more beneficial profile overall. Discussion: These results support the prebiotic role of polyphenols, showing how they are able to modulate the set of strains that comprises a genus in the gut, allowing them to adapt to a changing environment in the host's intestine and possibly exerting effects on its physiology.
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BACKGROUND: Patients undergoing rotator cuff repairs commonly experience postoperative pain and functional limitations. Various socioeconomic and pain-related factors have been recognized as influential in the prognosis of such patients. This study aims to investigate the associations between postoperative pain and functionality and preoperative pain-related outcomes and socioeconomic status in patients undergoing rotator cuff repairs. METHODS: This cross-sectional study examines the relationship between the outcomes of rotator cuff repairs and participants' socioeconomic status and pain-related measures. Socioeconomic status was assessed through indicators such as educational level, monthly household income, and occupation. Pain-related outcomes included measures of kinesiophobia and pain self-efficacy. RESULTS: A total of 105 patients (68 male, 37 female) were included in the analysis. The findings revealed no significant association between postoperative pain or functionality and the patients' socioeconomic status (p > 0.05). However, postoperative pain levels demonstrated a significant association with preoperative kinesiophobia (p < 0.05) and pain self-efficacy (p < 0.013). In contrast, functionality did not exhibit a significant association with these measures (p < 0.072 and 0.217, respectively). CONCLUSIONS: Preoperative pain-related outcomes play a role in postoperative pain levels among patients undergoing rotator cuff repairs. However, they do not appear to be related to functionality. Additionally, socioeconomic status does not significantly impact either pain or functionality.
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Purpose: This study aimedto determine a normative range of intraocular pressure (IOP) values measured with Icare rebound tonometer in premature infants and evaluate IOP variation over time and its correlation with the progression of postconceptional age (PCA). By doing so, we also evaluated advantages of this IOP-measuring method in this population when compared to more traditional methods. Methods: We conducted a single-center prospective study that included premature infants (gestational age ≤32 weeks) who were admitted to the neonatal intensive care unit (NICU) in Hospital Professor Doutor Fernando Fonseca. The study took place between January and December 2021. IOP was measured using Icare tonometer on the occasion of the first retinopathy of prematurity (ROP) screening requested by the NICU and again after a two-week interval if PCA was still ≤37 weeks. IOP measurements were stopped at 37 weeks or if the infant was discharged. The evaluated outcomes were mean IOP values and their correlation with PCA. Results: Thirty-four eyes of 17 preterm infants with a mean gestational age of 29.4 ± 2.3 weeks and a mean birth weight of 1222.9 ± 361.9 gr were evaluated. The mean IOP registered was 16.1 ± 6.4 mmHg, with a median value of 15.3 mmHg. The top 90th percentile was 22.1 mmHg and the bottom 10th percentile was 9.0 mmHg. The average IOP reduction was 4.8 ± 6.7 mmHg (P = 0.0019) within the two-week interval of PCA. Conclusion: The mean IOP in premature infants was 16.1 ± 6.4 mmHg and this value significantly decreased by 4.8 ± 6.7 mmHg every two weeks of PCA.
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Introduction: Some patients with rotator cuff injuries do not report significant changes in pain-related outcomes. Pain self-efficacy, which is commonly assessed using the Pain Self-Efficacy Questionnaire, may contribute toward this outcome. However, a Spanish adaptation of this questionnaire is currently lacking. Therefore, this study's purpose was developing the Spanish version of this questionnaire, and assess its psychometric properties. Methods: The Spanish version of the Pain Self-Efficacy Questionnaire was translated and culturally adapted, and a sample of 107 patients with rotator cuff injuries completed the questionnaire to examine its convergent validity (analyzing its correlation with the Tampa Scale of Kinesiophobia), its test-retest reliability, for which a subset of 40 participants completed again the questionnaire, and its internal consistency. Results: Translation was conducted without any problems, and 107 participants completed the study. Mean scores for the Pain Self-Efficacy Questionnaire were 45.2 points (standard deviation, 11.4). The Pain Self-Efficacy Questionnaire showed a moderate negative correlation with the Tampa Scale of Kinesiophobia (Pearson's correlation index r = -0.48) supporting its convergent validity. High test-retest reliability (Intraclass Correlation Coefficient of 0.90) and excellent internal consistency (Cronbach's α value of 0.92) were also found. Discussion: The Spanish version of the Pain Self-Efficacy Questionnaire presents high validity, test-retest reliability, and internal consistency to assess pain self-efficacy in patients suffering rotator cuff injuries in Spanish-speaking settings.
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OBJECTIVE: The objective of this study is to analyze conservative treatments implemented to manage positional plagiocephaly in infants. METHODS: This is a systematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, performed in the Medline (PubMed), Scopus, Web of Science, and Cochrane databases. Articles were selected according to the eligibility criteria, regarding the effectiveness of conservative treatments in positional plagiocephaly in infants, published in the last 10 years with a score ≥3 in the PEDro Scale. RESULTS: A total of 318 articles were identified and 9 of them were finally selected. CONCLUSIONS: Physical therapy treatment is considered as the first line of intervention in plagiocephaly with non-synostotic asymmetries and manual therapy is the method that obtains the best results within this intervention. In cases of moderate or severe plagiocephaly, helmet therapy can be an effective second-line intervention; however, the best way to prevent this condition is through counseling of parents or caregivers, and early treatment is essential for optimal therapeutic outcomes. The review was registered in PROSPERO (CDR42022306466).
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Sexual health is crucial for overall well-being, and dyspareunia (genito-pelvic pain/penetration disorder) is a common sexual disorder that can be addressed through multimodal physiotherapy approaches, including education. However, it's unclear whether socioeconomic factors influence the effectiveness of educational therapies for dyspareunia. The dataset presented in this article was used in a pilot randomized controlled trial that aimed to investigate any potential correlation between socioeconomic status and the outcomes of a therapeutic educational program for dyspareunia, evaluating the impact of a therapeutic educational program on 69 women. The data measured pain intensity, pain-related outcomes, and sexual functioning over time. In February 2022, socioeconomic status measurements (age, educational level, household monthly income, and job rank) were collected. The analysis used Pearson's correlation index and Spearman's rho statistic to assess any correlations between these variables. The results of the correlation analysis indicated that there was no significant correlation between any of the outcomes of the intervention and the socioeconomic status measurements. The data analysis findings suggest that a therapeutic educational program can effectively improve pain intensity, pain-related outcomes, and sexual functioning in patients with persistent pelvic pain, regardless of their socioeconomic status. These findings have policy implications, as they suggest that education is a powerful tool that can improve sexuality outcomes for patients with dyspareunia, regardless of their socioeconomic background. The dataset contains the collected raw data, including partial participant demographics data and scores categorized by question group, as well as scores for each participant at each time point (before and after the intervention). This dataset can be used to further analyze the results and the study can be potentially replicated.
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Aim: This study evaluates the safety and efficacy of micropulse transscleral cyclophotocoagulation (MPTSCPC) in glaucoma patients, with standard parameters, over a 24-month period. Methods: Retrospective analysis of 61 eyes undergoing MPTSCPC from January 2018 to December 2020 was carried out. Patients received 160 seconds of laser, with settings of 2000 mW/cm2 and a duty cycle of 31.3%. Results: A total of 61 eyes were included, arranged in an age distribution of 73.9 ± 10.8 years. The most frequent diagnosis was primary open-angle glaucoma (POAG), with a mean best-corrected visual acuity (BCVA) of 5/10 in the Snellen Visual chart. Around 37.7% of the eyes had undergone at least one glaucoma filtration surgery prior to MPTSCPC. The mean pretreatment intraocular pressure (IOP) was 24.9 ± 8.6 mm Hg. Except for the contrast at 24 months, at every other follow-up visit, there was a significant reduction (p ≤ 0.001) in IOP and in the number of topical drugs required to control IOP, from four (baseline) to three, with oral acetazolamide suspension in most cases. The total success rate (absolute and clinical successes combined) was 81.9% after 1 year of the treatment. There was no drop in visual acuity or cases of serious complications. There is a positive and significant correlation between prior glaucoma surgery and the need for reinterventions (p = 0.028). Conclusions: Micropulse transscleral cyclophotocoagulation (MPTSCPC) is an effective and safe procedure for reducing IOP within a broad spectrum of glaucoma patients. Additional studies are needed to confirm the current indications, widen their scope, and determine the optimal treatment settings on an individual basis. How to cite this article: Basto RC, Almeida J, Roque JN, et al. Clinical Outcomes of Micropulse Transscleral Cyclophotocoagulation: 2 Years of Experience in Portuguese Eyes. J Curr Glaucoma Pract 2023;17(1):30-36.
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Reduced bone mineral density (BMD), osteoporosis, and their associated fractures are one of the main musculoskeletal disorders of the elderly. Quickness in diagnosis could prevent associated complications in these people. This study aimed to perform a systematic review (SR) to analyze and synthesize current research on whether a calcaneal quantitative ultrasound (QUS) can estimate BMD and predict fracture risk in elderly people compared to dual-energy x-ray absorptiometry (DXA), following the PRISMA guidelines. A search was conducted in the main open-access health science databases: PubMed and Web of Science (WOS). DXA is the gold standard for the diagnosis of osteoporosis. Despite controversial results, it can be concluded that the calcaneal QUS tool may be a promising method to evaluate BMD in elderly people, facilitating its prevention and diagnosis. However, further studies are needed to validate the use of calcaneal QUS.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Biomarkers for ALS are essential for disease detection and to provide information on potential therapeutic targets. Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or substrates such as neuropeptides. Since certain aminopeptidases are known to increase the risk of neurodegeneration, such mechanisms may reveal new targets to determine their association with ALS risk and their interest as a diagnostic biomarker. The authors performed a systematic review and meta-analyses of genome-wide association studies (GWASs) to identify reported aminopeptidases genetic loci associated with the risk of ALS. PubMed, Scopus, CINAHL, ISI Web of Science, ProQuest, LILACS, and Cochrane databases were searched to retrieve eligible studies in English or Spanish, published up to 27 January 2023. A total of 16 studies were included in this systematic review, where a series of aminopeptidases could be related to ALS and could be promising biomarkers (DPP1, DPP2, DPP4, LeuAP, pGluAP, and PSA/NPEPPS). The literature reported the association of single-nucleotide polymorphisms (SNPs: rs10260404 and rs17174381) with the risk of ALS. The genetic variation rs10260404 in the DPP6 gene was identified to be highly associated with ALS susceptibility, but meta-analyses of genotypes in five studies in a matched cohort of different ancestry (1873 cases and 1861 control subjects) showed no ALS risk association. Meta-analyses of eight studies for minor allele frequency (MAF) also found no ALS association for the "C" allele. The systematic review identified aminopeptidases as possible biomarkers. However, the meta-analyses for rs1060404 of DPP6 do not show a risk associated with ALS.
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Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/genética , Aminopeptidases , Estudo de Associação Genômica Ampla , Prognóstico , BiomarcadoresRESUMO
"Watch and wait" is becoming a common treatment option for patients with locally advanced rectal cancer (LARC) submitted to neoadjuvant treatment. However, currently, no clinical modality has an acceptable accuracy for predicting pathological complete response (pCR). The aim of this study was to assess the clinical utility of circulating tumor DNA (ctDNA) in predicting the response and prognosis in these patients. We prospectively enrolled a cohort of three Iberian centers between January 2020 and December 2021 and performed an analysis on the association of ctDNA with the main response outcomes and disease-free survival (DFS). The rate of pCR in the total sample was 15.3%. A total of 24 plasma samples from 18 patients were analyzed by next-generation sequencing. At baseline, mutations were detected in 38.9%, with the most common being TP53 and KRAS. Combination of either positive magnetic resonance imaging (MRI) extramural venous invasion (mrEMVI) and ctDNA increased the risk of poor response (p = 0.021). Also, patients with two mutations vs. those with fewer than two mutations had a worse DFS (p = 0.005). Although these results should be read carefully due to sample size, this study suggests that baseline ctDNA combined with mrEMVI could potentially help to predict the response and baseline ctDNA number of mutations might allow the discrimination of groups with different DFS. Further studies are needed to clarify the role of ctDNA as an independent tool in the selection and management of LARC patients.